Single-cell transcriptomics reveals CD8+ T cell structure and developmental trajectories in idiopathic pulmonary fibrosis

Abstract

Immune cells in the human lung are associated with idiopathic pulmonary fibrosis. However, the contribution of different immune cell subpopulations to the pathogenesis of pulmonary fibrosis remains unclear. We used single-cell RNA sequencing data to investigate the transcriptional profiles of immune cells in the lungs of 5 IPF patients and 3 subjects with non-fibrotic lungs. In an identifiable population of immune cells, we found increased percentage of CD8⁺ T cells in the T cell subpopulation in IPF. Monocle analyzed the dynamic immune status and cell transformation of CD8⁺ T cells, as well as the cytotoxicity and exhausted status of CD8⁺ T cell subpopulations at different stages. Among CD8⁺ T cells, we found differences in metabolic pathways in IPF and Ctrl, including lipid, amino acid and carbohydrate metabolic. By analyzing the metabolites of CD8⁺ T cells, we found that different populations of CD8⁺ T cells in IPF have unique metabolic characteristics, but they also have multiple identical up-regulated or down-regulated metabolites. In IPF, signaling pathways associated with fibrosis were enriched in CD8⁺ T cells, suggesting that CD8⁺ T cells may have an important contribution to fibrosis. Finally, we analyzed the interactions between CD8⁺ T cells and other cells. Together, these studies highlight key features of CD8⁺ T cells in the pathogenesis of IPF and help to develop effective therapeutic targets.